Asymmetric Synthesis of 3,5-Substituted Hydantoins via an aza-Heck Cyclization


  • Montana Edwards, Biochemistry, University of Delaware

Faculty Mentor(s)

  • Donald Watson, Chemistry and Biochemistry, University of Delaware


Nitrogen-containing heterocycles are versatile molecules for the synthesis of natural products
and bioactive molecules. Aza-Heck cyclizations intramolecularly couple an electrophilic nitrogen source
with a tethered alkene to form a variety of nitrogen heterocycles. Asymmetric nitrogen heterocycles are
especially desired for medicinal chemistry, as they allow access to unique drug structures. Hydantoins
are oxidized derivatives of imidazolidines and are highly integral for the formation of a variety of
medications, including anticonvulsants. In addition, asymmetric hydantoins are the precursor to many
naturally occurring amino acids. While symmetric hydantoin synthesis is widely explored and used for
medicinal purposes, enantiospecific synthetic pathways are underdeveloped. This project utilizes a
palladium catalyst with stereospecific, chiral ligands, to form one enantioselective product. Our
asymmetric aza-Heck reaction allows for high enantiomeric excess, %ee, which describes the asymmetry
of the products. Herein, I describe the work I have completed throughout this summer: expanding upon
my work over the last two years to form a variety of these asymmetric hydantoins and preparing our
paper for publication.